Excess Female Siblings and Male Fetal Loss in Families with Systemic Lupus Erythematosus

Abstract

Objective.Systemic lupus erythematosus (SLE) occurs more frequently among women than men. We aimed to determine whether the male-female ratio in SLE families is different from what would be expected by chance, and whether excess male fetal loss is found.Methods.All patients with SLE met the revised American College of Rheumatology classification criteria, while unaffected subjects were shown not to satisfy these same criteria. Putative family relationships were confirmed by genetic testing. Pregnancy history was obtained from all subjects, including unrelated control women. Adjusted Wald binomial confidence intervals were calculated for ratio of boys to girls in families and compared to the expected ratio of 1.06.Results.There were 2579 subjects with SLE, with 6056 siblings. Considering all subjects, we found 3201 boys and 5434 girls (ratio 0.59, of 95% CI 0.576–0.602). Considering only the SLE-unaffected siblings, there were 2919 boys and 3137 girls (ratio 0.93, 95% CI 0.92–0.94). In both cases, the ratio of males to females was statistically different from the known birth rate. Among patients with SLE as well as among their sisters and mothers, there was an excess of male fetal loss compared to the controls.Conclusion.Siblings of patients with SLE are more likely than expected to be girls. This finding may be in part explained by excess male fetal loss, which is found among patients with SLE and their first-degree relatives.